Ewa Lech-Maranda^1,2, Jacques Bienvenu^1,4, Anne-Sophie Michallet³, Roch Houot³, Tadeusz Robak², Bertrand Coiffier^1,3, Gilles Salles^1,3

European Cytokine Network, Vol.17, No.1, pp. 60-66, 2006

Abstract The aim of the study was to confirm whether plasma levels of interleukin-10 (IL-10) correlate with the prognosis in diffuse, large B-cell lymphoma (DLBCL) patients. Plasma IL-10 levels were determined at the time of diagnosis in a group of 157 consecutively treated, DLBCL patients. Of those, 122 patients (78%) had IL-10 plasma levels below the detection limit (< 5 pg/mL) and 35 (22%) above this value. The median value for patients with detectable IL-10 levels was 35 pg/mL (range, 5 to 2480 pg/mL). Detectable plasma IL-10 levels were significantly associated with age > 60 years,… More >

Andrew E. Strong¹, Anne-Christine Thierry², Pascal Cousin³, Corinne Moulon⁴, Stéphane Demotz⁵

European Cytokine Network, Vol.17, No.1, pp. 49-59, 2006

Abstract Chemokines constitute a protein family that exhibit a variety of biological activities involved in normal and pathological physiological processes. CCL11 (eotaxin), CCL19 (MIP-3b), CCL22 (MDC), CXCL11 (I-TAC) and CXCL12 (SDF-1a) chemokines, modified with the Alexa Fluor^® 647 fluorescent dye at specific positions along their sequence, were produced by a chemical route and their biological activities were characterized. In a migration assay, fluorescent chemokines were as biologically active as the unmodified forms. All labeled chemokines specifically stained cell lines transfected with the appropriate human chemokine receptors. The specificity of binding was further established by showing that the… More >

Angela Garau¹, Riccardo Bertini², Marco Mosca², Cinzia Bizzarri², Roberto Anacardio², Sara Triulzi¹, Marcello Allegretti², Pietro Ghezzi¹, Pia Villa^1,3

European Cytokine Network, Vol.17, No.1, pp. 35-41, 2006

Abstract The chemokine receptors CXCR1 and CXCR2 present on polymorphonuclear neutrophils (PMN), bind the chemokine CXC ligand 8 (CXCL8)/interleukin-8 (IL-8), and have a key role in PMN recruitment in inflammation. Based on the structure of reparixin, a small-molecular-weight allosteric inhibitor of CXCR1, we designed a dual inhibitor of CXCR1 and CXCR2 with a longer in vivo half-life, DF2156A. This molecule inhibited human and rat PMN migration in response to CXCR1 and CXCR2 ligands and showed an elimination half-life following i.v. administration, of 19 hours. In a rat model of cerebral ischemia/reperfusion induced by temporary (90 min) More >

Elena Westphal^1,*, Mona Herzberg^2,*, Ingo Neumann^1,**, Li Beibei¹, Claudia Pilowski¹, Chen Li¹, Karl Werdan¹, Harald Loppnow^1,2

European Cytokine Network, Vol.17, No.1, pp. 19-28, 2006

Abstract Inflammation contributes to the pathogenesis of atherosclerosis. Proinflammatory cytokines, including interleukin-1 (IL-1), may be involved in the local inflammation occurring in the vessel wall. Vascular smooth muscle cells express the unprocessed IL-1β precursor molecule. Invading leukocytes, such as monocytes or polymorphonuclear granulocytes (PMN) may activate the IL-1β precursor during atherogenesis. Thus, we investigated the capacity of PMN to process IL-1β and IL-18 precursors. Processing was analyzed using Western blot and bioassay for IL-1-activity was performed. As few as 80 to 400 PMN/mL detectably processed preIL-1β. PMN also cleaved the caspase-1 substrate preIL-18. The preIL-1β and… More >

Ying Gao¹, Hans Tapper², Jero Calafat³, Inge Olsson¹, Markus Hansson¹

European Cytokine Network, Vol.17, No.2, pp. 98-108, 2006

Abstract In this experiment, we explored the potential of secretory lysosomes of hematopoietic cells to act as vehicles for immunomodulatory protein delivery at an inflammation site. We investigated whether exogenous soluble TNF-receptor 1 (sTNFR1) could be expressed in primary hematopoietic progenitor cells and become targeted for storage and secretion during granulopoietic differentiation. An sTNFR1 construct with a transmembrane domain (tm) and a cytosol sorting signal (Y) taken from CD63, was retrovirally transduced to lineage-negative murine hematopoietic bone marrow stem/progenitor cells. This process was followed by cytokine-driven granulopoietic maturation. The sTNFR1-tm-Y was found to be synthesized in… More >

Hubertus Himmerich^1,2, Stephany Fulda¹, Jakob Linseisen^3,4, Henrike Seiler³, Günther Wolfram⁵, Stephanie Himmerich⁶, Kurt Gedrich⁶, Thomas Pollmächer^1,7

European Cytokine Network, Vol.17, No.3, pp. 196-201, 2006, DOI:10.1684/ecn.2006.0037

Abstract The cytokines tumor necrosis factor-a (TNF-α), soluble TNF receptors p55 and p75, and interleukin 6 (IL-6) are involved in host defense against several microbiological agents, in the process of inflammation and also in body weight regulation. In the present study, we sought to assess the influence of age, gender, smoking, and body mass index on plasma levels of TNF-α, TNF receptors, and IL-6 in more than 550 adult subjects randomly selected from the Bavarian population. None of the cytokine parameters had a normal distribution and all distributions were significantly skewed. The cytokine plasma levels investigated More >

Yvonne Kalmbach^1,2, Angelica B. W. Boldt¹, Rolf Fendel^1,2, Benjamin Mordmüller^1,2, Peter G. Kremsner^1,2, Jürgen F. J. Kun¹

European Cytokine Network, Vol.17, No.3, pp. 175-180, 2006, DOI:10.1684/ecn.2006.0032

Abstract The outcome of a Plasmodium falciparum infection differs greatly between patients, ranging from an asymptomatic carrier status to the most severe characteristics influenced by activating and inhibiting immune factors. The inhibitory leukocyte immunoglobulin-like receptor (LILRB1/CD85j) plays an important role in the immune response as regulator of cytotoxic T cells and of premature activation and clonal expansion of B cells. To investigate its role in malaria, we analyzed blood samples from malaria patients by cytometric analysis. We found a similar expression pattern of CD85j on PBMC in both patients and healthy children. However, malaria patients presented significantly More >

Ettore Capoluongo¹, Dario Pitocco², Concetta Santonocito¹, Paola Concolino^1,3, Stefano Angelo Santini^1,3, Andrea Manto², Paola Lulli¹, Giovanni Ghirlanda², Cecilia Zuppi¹, Franco Ameglio¹

European Cytokine Network, Vol.17, No.3, pp. 164-174, 2006, DOI:10.1684/ecn.2006.0036

Abstract Background. Patients with type 1 diabetes (T1DM) present lower serum free IGF and IGFBP-3 values than healthy people. T1DM patients often present with associated autoimmune diseases such as thyroiditis or coeliac disease, and over time they frequently develop proliferative retinopathy, neuropathy or nephropathy in different combinations. Objective. The aim of this study was to evaluate the effect of two associated autoimmune diseases or three diabetic complications on the serum free IGF-I or IGFBP-3 levels in T1DM patients, who also have a family history of T1DM. Design. 246 T1DM patients were enrolled, and then subdivided into… More >

Amel Boumendjel^1,2, Lina Tawk¹, René de Waal Malefijt³, Vera Boulay¹, Hans Yssel¹, Jérôme Pène¹

European Cytokine Network, Vol.17, No.4, pp. 281-289, 2006, DOI:10.1684/ecn.2006.0045

Abstract It has been reported that IL-27 specifically induces the production of IgG2a by mouse B cells and inhibits IL-4-induced IgG1 synthesis. Here, we show that human naïve cord blood expresses a functional IL-27 receptor, consisting of the TCCR and gp130 subunits, although at lower levels as compared to naïve and memory splenic B cells. IL-27 does not induce proliferative responses and does not increase IgG1 production by CD19⁺ CD27⁺ memory B cells. However, it induces a low, but significant production of IgG1 by naïve CD19⁺ CD27^– IgD⁺ IgG^– spleen and cord blood B cells, activated via CD40, whereas… More >

Emmanouil Galanakis, Francescopaolo Di Cello, Maneesh Paul-Satyaseela, Kwang Sik Kim

European Cytokine Network, Vol.17, No.4, pp. 260-265, 2006, DOI:10.1684/ecn.2006.0042

Abstract Microbial penetration of the blood-brain barrier (BBB) into the central nervous system is essential for the development of meningitis. Considerable progress has been achieved in understanding the pathophysiology of meningitis, however, relatively little is known about the early inflammatory events occurring at the time of bacterial crossing of the BBB. We investigated, using real-time quantitative PCR, the expression of the neutrophil chemoattractants alpha-chemokines CXCL1 (Groa) and CXCL8 (IL-8), and of the monocyte chemoattractant beta-chemokine CCL2 (MCP-1) by human brain microvascular endothelial cells (HBMEC) in response to the meningitis-causing E. coli K1 strain RS218 or its isogenic… More >